title: IL-17 attenuates degradation of ARE-mRNAs by changing the cooperation between AU-binding proteins and microRNA16.
abstract: Interleukin 17A (IL-17), a mediator implicated in chronic and severe inflammatory diseases, enhances the production of pro-inflammatory mediators by attenuating decay of the encoding mRNAs. The decay of many of these mRNAs depends on proteins (AUBps) that target AU-rich elements in the 3'-untranslated region of mRNAs and facilitate either mRNA decay or stabilization. Here we show that AUBps and the target mRNA assemble in a novel ribonucleoprotein complex in the presence of microRNA16 (miR16), which leads to the degradation of the target mRNA. Notably, IL-17 attenuates miR16 expression and promotes the binding of stabilizing AUBps over that of destabilizing AUBps, reducing mRNA decay. These findings indicate that miR16 independently of a seed sequence, directs the competition between degrading and stabilizing AUBps for target mRNAs. Since AUBps affect expression of about 8% of the human transcriptome and miR16 is ubiquitously expressed, IL-17 may in addition to inflammation affect many other cellular processes.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands ; Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Saheli
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Annemiek
authors.initials: A
authors.lastname: Dijkhuis
authors.forename: Sabrina
authors.initials: S
authors.lastname: Steiert
authors.forename: René
authors.initials: R
authors.lastname: Lutter
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D063307:AU Rich Elements / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D011485:Protein Binding; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D020381:Interleukin-17; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase